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Rights statement: This is an author manuscript that has been accepted for publication in Journal of General Virology but has not been copy-edited, formatted or proofed. Cite this article as appearing in Journal of General Virology. This version of the manuscript may not be duplicated or reproduced, other than for personal use or within the rule of 'Fair Use of the Copyrighted Materials' (Section 17, Title 17, US Code). The final publisher version can be found at: http://vir.sgmjournals.org/content/early/2013/10/12/vir.0.058958-0

Abstract

The occurrence of variant Creutzfeldt-Jacob disease (vCJD) in humans was almost certainly the result of consumption of food contaminated with bovine spongiform encephalopathy (BSE) prions. Despite probable widespread exposure of the UK population to BSE-contaminated food in the 1980s, vCJD has predominantly been identified in young individuals, and there have been fewer cases of clinical disease than anticipated. The reasons for this are uncertain. Following peripheral exposure many prions replicate within the lymphoid tissues before infecting the CNS. We have shown that the effects of host age on the microarchitecture of the spleen significantly impair susceptibility to mouse-adapted prions after peripheral exposure. The transmission of prions between different mammalian species is considered to be limited by the "species barrier," which is dependent on several factors including an intact immune system. Thus, cross-species prion transmission may be much less efficient in aged individuals. To test this hypothesis, we compared prion pathogenesis in groups of young (six to eight weeks old) and aged (600 d old) mice injected with primary BSE. We show that prion pathogenesis was dramatically impaired in aged mice when compared to young animals. Whereas most young mice succumbed to clinical prion disease, all aged mice failed to develop clinical disease during their lifespans. However, the demonstration that prion accumulation was detected in the lymphoid tissues of some aged mice after injection with primary BSE, in the absence of clinical signs of prion disease, has important implications for human health.